GIST Opens Possibility for Developing Non-Alcoholic Fatty Liver Disease Treatment

[Asia Economy Honam Reporting Headquarters, Reporter Yoon Jamin] The possibility of developing a treatment for nonalcoholic fatty liver disease has opened.

The research team led by Professor An Jinhee of the Department of Chemistry at Gwangju Institute of Science and Technology (President Kim Kiseon·GIST) announced on the 20th that they have developed a serotonin (5HT) receptor inhibitor (a substance that inhibits the catalytic action of enzymes, an inverse catalyst) for peripheral tissues.

Fatty liver, characterized by the accumulation of more than 5% fat in liver cells, usually shows almost no symptoms but can progress to cirrhosis or worsen to steatohepatitis. When it advances to cirrhosis, the incidence of liver cancer increases. In particular, nonalcoholic fatty liver disease (NAFLD) is caused by obesity, diabetes, metabolic syndrome, etc., and is increasing worldwide.

However, there are currently no approved drugs for the treatment of nonalcoholic fatty liver disease, making the development of treatments urgent.

Serotonin is a well-known neurotransmitter that regulates appetite in the central nervous system but is known to be involved in maintaining energy homeostasis in peripheral tissues.

Professor An’s research team confirmed that when the compound was administered to mice fed a high-fat diet, liver weight decreased and fat accumulation in the liver was reduced. Accordingly, this candidate substance is expected to be used as a treatment for nonalcoholic fatty liver disease.

The research team aimed to find a new compound acting on peripheral tissues from Pimavanserin, a known serotonin 2 receptor (5HT2A) inhibitor and a Parkinson’s disease-related psychiatric drug approved by the FDA in 2016.

As a result, they found a compound (IC50* = 8.35 nM) that reduces blood-brain barrier penetration, mainly acts on peripheral tissues, and has excellent efficacy.

This compound showed good microsomal stability in the liver and did not inhibit CYP or hERG. Additionally, testing its efficacy on eight other serotonin receptors confirmed that it selectively inhibits 5HT2A.

In animal experiments conducted for 10 weeks on mice fed a high-fat diet with this compound, fat accumulation and hepatic steatosis in the liver were alleviated, glucose tolerance improved, and liver weight decreased.

Professor An said, “This research outcome is expected to be used for discovering new targets and developing treatments for nonalcoholic fatty liver (inflammation), contributing to future related new drug development.”

Meanwhile, this study conducted by GIST Professor An Jinhee (corresponding author) was supported by the Ministry of Science and ICT and the Ministry of Health and Welfare, and the related paper was published online on the 14th in the Journal of Medicinal Chemistry, a prestigious international journal in the field of medicinal chemistry published by the American Chemical Society.

This content was produced with the assistance of AI translation services.